PPAR-γ Activation Alleviates Intestinal Dysfunction and Lactose Malabsorption in Experimental Food Allergy Rats

Food allergy-induced intestinal inflammation can impair lactose digestion and absorption by damaging the epithelium, leading to secondary lactase deficiency with no effective treatments. The immunometabolism nuclear receptor PPAR-γ regulates gut epithelial function and nutrient absorption. This study aimed to determine whether PPAR-γ activation can preserve lactose digestion and absorption during allergic inflammation and to elucidate the underlying mechanisms.

In an ovalbumin-sensitized Brown Norway rat model of food allergy, animals were treated with either the PPAR-γ agonist rosiglitazone or the antagonist GW9662. Lactose absorption was assessed by in vivo lactose tolerance tests (blood glucose monitoring) and intestinal transit measurements. Jejunal tissues were analyzed for lactase gene expression, lactase enzyme activity, and SGLT1/GLUT2 transporter levels.

Allergic rats exhibited reduced weight gain, delayed intestinal transit, and lactose malabsorption (lower blood glucose after lactose challenge), accompanied by sharply decreased jejunal lactase mRNA, enzyme activity, and SGLT1/GLUT2 levels. Rosiglitazone treatment restored intestinal PPAR-γ expression and markedly improved lactose absorption, normalizing the lactose tolerance curve. Rosiglitazone also increased lactase gene expression and enzyme activity, and upregulated SGLT1 levels. In contrast, PPAR-γ inhibition with GW9662 further reduced lactase and transporter levels and failed to improve absorption.

PPAR-γ signaling maintains intestinal lactose digestive capacity of rats during allergic inflammation by sustaining lactase production and monosaccharide transporter expression. Our findings verify an immunometabolism mechanism linking nuclear receptor activation to enhanced nutrient absorption and highlight PPAR-γ agonism as a promising therapeutic strategy to alleviate food allergy-associated lactose malabsorption.